Until now there has been a distinct lack of a truly representative breast cancer model. The development of a complex heterologous multi-compartment xenograft model incorporating the relevant stromal elements will provide a realistic alternative to currently available chimeric xenograft models. The recent ability to immortalize primary human mammary endothelial cells and fibroblasts by the insertion of the hTERT and a temperature sensitive mutant variant of SV40 LT has made this possible. We have commenced the development of an organotypic, 3-compartment xenograft model of human breast cancer. The immortalized mammary stromal cells provide a viable and much needed tumour microenvironment of human origin for tumour proliferation. Results have confirmed the crucial importance of stromal cell support as well as tumour-stromal interactions in tumourigenesis. MCF-7 cells when xenografted in numbers insufficient to produce tumours alone, consistently produced tumours when combined with stromal cells. Also, heterologous xenografts produced not only faster growing but larger tumours than tumour cell lines alone. Immunohistochemical analysis using human cell specific markers demonstrated that initial tumour growth was supported by the stromal cells before the recruitment of host vasculature. The xenografts were composed predominantly of proliferating tumour cells, host ECM and vasculature. Surprisingly the LT antigen expressing immortalized stromal cells did not survive, proliferate or form organized structures in this environment for any reasonable time period. To conclude, these findings parallel observations made in 3-D organotypic cultures which indicates that progression of the epithelial cell tumour is not cell autonomous. Rather, that tumourigenesis is promoted, and probably sometimes induced, by the anomalies in the surrounding stroma and microenvironment. With further refinement and adjustments this model can be utilized as a credible pre-clinical model for the development and testing of new therapeutic strategies, such as those that target breast cancer stroma itself. This is very timely as stroma is now emerging as the dominant factor in modulating epithelial morphogenesis and mitogenesis.

Aims: The main objective of this research was to compare psychological distress (anxiety and depression) and body image dissatisfaction (BID) between two groups of women: those who had undergone breast reconstruction following mastectomy for breast cancer (BR) and those who had undergone breast reconstruction and additional procedures (BR-AP). Furthermore, the study aimed to explore the possible reasons why women might undergo additional procedures following breast reconstruction. Method: A cross-sectional retrospective design was employed and data was collected at one time period only. Ninety seven patients were recruited (69.3% of the total patient cohort) who attended prearranged clinic appointments between August 2006 and February 2007 at a regional Breast Care Unit. Results: The prevalence of anxiety and depression was higher in the BR-AP group compared to the BR group. This difference was not significant for anxiety, however it was approaching statistical significance for depression (p = 0.09). The BR-AP group had a significantly higher BID than the BR group (p = 0.045). There was some evidence that undergoing additional procedures predicted depression (p = 0.060) and BID (p = 0.045). Conclusions: Undergoing additional procedures following breast reconstruction may not lead to a positive psychological outcome in terms of anxiety, depression and body image dissatisfaction. In view of the cost that undergoing these procedures presents to the NHS, coupled with the assumption that they offer psychological benefits, further research that prospectively examines psychological aspects of women seeking additional procedures is strongly recommended. Knowledge gained from such research is likely to assist in the pre-operative assessment of these women.

Following mastectomy for breast cancer a wide variety of surgical techniques are currently available for post mastectomy breast reconstruction where autologous tissue is used to construct a natural looking breast. One of the most common types of reconstructive surgeries use Deep Inferior Epigastric Perforator (DIEP) free flap where skin and adipose tissue along with their blood supplies are transferred from the lower abdomen to the chest. The success of free flap reconstructive surgery depends strongly on the maintenance of adequate perfusion in the flap. Early diagnosis of ischaemia and surgical exploration to restore blood flow can often salvage the flap and may prevent graft failure. Even though many techniques have been used, there is still a need to develop a non-invasive, easy to use, reproducible and inexpensive monitoring device to assess flap perfusion. In an attempt to overcome the limitations of the current flap perfusion monitoring techniques a prototype reflectance three wavelength photoplethysmographic (PPG) sensor was developed. The PPG sensor consisted of two infrared (940 nm), two green (520 nm) and two red (660 nm) LEDs and a photodiode. A PPG processing system was also constructed in order to drive the optical components on the sensor and to detect and pre-process the PPG signals. A Virtual Instrument (VI) was also implemented in LabVIEW in order to display, analyse and archive the PPG signals with the capability of real-time estimation of arterial oxygen saturation (SpO2) values. The system was evaluated in a pilot study on fifteen patients undergoing breast reconstructive surgery using (DIEP) flaps. Good quality red, infrared and green PPG signals were obtained pre-operatively from the donor site (abdomen), intra-operatively (capturing reperfusion of flap following anastomosis) and post-operatively at regular intervals for up to 12 hours post surgery. SpO2 values were also estimated which were found to be in broad agreement with SpO2 values recorded from the commercial pulse oximeter attached to the patients’ finger. The flap PPGs were compared with PPGs and SpO2s acquired from the finger of a small number of patients using a custom made reflectance finger PPG probe, optically and electrically, identical as the flap probe. The finger PPGs were found to be much larger than the flap PPGs which confirms the hypothesis of inadequate perfusion in the flap during and after the operative period. Furthermore the custom made PPG processing system and flap sensor were used successfully on a series of case studies to evaluate the versatility of the system in monitoring PPG signals and estimating blood oxygen saturation in other flaps. These included monitoring two patients undergoing Latissimus Dorsi (pedicle) flap reconstructive surgery and a head and neck free flap surgery where a Vertical Rectus Abdominis Myocutaneous (VRAM) flap was used following total petrosectomy. Also, two patients undergoing reconstructive surgery of the oesophagus using jejunum free flaps were also recruited into the study. For this study a purpose build oesophageal PPG sensor was developed. These case studies demonstrated the ability to use the developed PPG sensors to acquire PPG signals and estimate SpO2s in a variety of flaps. The results have confirmed that the custom made PPG system and sensor has the potential to be used as an alternative technique for monitoring perfusion in various types of flaps at all operative periods.